Potassium Carbonate → 4-{6-[2-fluoro-4-(2-hydroxy-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 1036817노트

반응식

HRID 1036817 반응식
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C([Si](C)(C)[O:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[C:32]([F:37])[CH:31]=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.C1COCC1.O>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([O:36][C:33]3[CH:34]=[CH:35][C:30]([CH2:29][CH2:28][OH:27])=[CH:31][C:32]=3[F:37])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 114933574-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl esterHCID 672032794-[2-(Tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-phenol

생성물 1

HCID 598567524-{6-[2-fluoro-4-(2-hydroxy-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl Ester수율 89%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (270 mg, 0.84 mmol) and 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-phenol (279 mg, 0.84 mmol) in DMF (5 mL), was K2CO3 (137 mg, 0.84 mmol) added. The reaction mixture was irradiated under microwave for 1 hour at 150° C. The reaction was cooled to room temperature and treated with 1.0 M TBAF in THF (0.9 mL). After stirring for 2 hours, the reaction was poured into H2O (50 mL) and extracted with ethyl acetate (50 mL). The ethyl acetate was dried over MgSO4, and concentrated under vacuum and purified over SiO2 to afford the desired compound (321 mg, 89%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (s, 1H), 7.38˜7.37 (m, 1H), 7.29˜7.28 (m, 1H), 7.21˜7.17 (m, 1H), 5.30 (m, 1H), 4.75 (m, 1H), 3.67˜3.65 (m, 2H), 3.64˜3.41 (m, 2H), 3.33˜3.30 (m, 2H), 3.02 (m, 2H), 2.91 (s, 3H), 1.99˜1.93 (m, 2H), 1.66˜1.64 (m, 2H), 1.22 (d, 6H). LCMS 432.6 [MH+].

후처리

  1. additionadded
  2. customThe reaction mixture was irradiated under microwave for 1 hour at 150° C
  3. extractionextracted with ethyl acetate (50 mL)
  4. dry with materialThe ethyl acetate was dried over MgSO4
  5. concentrationconcentrated under vacuum
  6. custompurified over SiO2

출처 및 근거

ORD 기록
ord-619c95b1ace84e8f8c6bc3d666f829b6
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546429B2

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